Fasting, Exercise, and Diet to Activate Autophagy in Depression
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-40
SponsorUniversity of Zurich
About this trial
Depression is a common mental health condition that affects millions of people worldwide and is a leading cause of disability. Although current treatments can be effective, many patients do not fully recover or experience long-term improvement. This study aims to better understand how lifestyle factors such as physical activity and diet-related processes may influence biological mechanisms that could be linked to depression.
The study focuses on a natural cellular process called autophagy, which helps cells remove damaged components and maintain healthy function. Autophagy is influenced by energy availability in the body and may be affected by behaviors such as physical exercise and caloric restriction. Early evidence suggests that changes in autophagy may also be linked to mood regulation and depression, but this relationship is not yet well understood in humans.
In this exploratory study, we will investigate how physical activity influences autophagy and related metabolic and molecular processes in healthy adults. We will also examine whether these effects differ between individuals with different body weight and fitness levels, and between women and men.
A total of approximately 120 healthy adults aged 18 to 40 years will participate. Participants will be divided into four groups based on sex and body weight (normal weight or overweight). Each participant will attend study visits at the University Hospital Zurich and perform a standardized cycling exercise test under medical supervision.
During the exercise test, participants will perform a graded cycling protocol that gradually increases in intensity until exhaustion. We will collect small blood samples from a vein and from a fingertip at several time points before, during, and after exercise. Saliva samples will also be collected to measure stress-related hormones. Additional measurements include heart rate, breathing parameters, oxygen consumption, and physical performance.
Blood and saliva samples will be analyzed using advanced laboratory techniques to study changes in metabolism, immune signaling, hormones, gene activity, and markers related to autophagy. These analyses will help identify biological pathways that are activated by exercise and may be relevant to brain health and depression.
Participants will undergo medical screening before inclusion to ensure safety. Individuals with certain medical conditions or factors that could interfere with the study results will not be included. Participation is voluntary, and participants may withdraw at any time without consequences.
The study involves minimal risks associated with blood sampling and intense physical exercise, which will be performed under close medical supervision. The expected benefit is improved scientific understanding of how lifestyle-related biological processes may be linked to mental health, which could support the development of new preventive or therapeutic strategies for depression in the future.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
age: 18-40 years
BMI: between 18.5 and 24.9 kg/m2 (SG1/2) or BMI between 25.0 and 39.9 kg/m2 (SG3/4)
ability to understand the study procedure and give consent
Written informed consent
Disqualifiers
No infectious illness for at least two weeks prior to the test
No vitamin supplementation during the week prior to the performance test
SG3 and SG4: More than 1 hour moderate exercise per week
No use of hormonal contraceptives in the last 6 months before the onset of the study (SG1/3)
Trial design
Design model
Parallel
Treatments tested in this trial
Performance test
Procedure/SurgeryStandardized CPET on a bicycle ergometer. Venous and capillary blood sampling at baseline (rest), end of aerobic warm-up phase (15 min), peak exercise (ramp-protocoll, 8-12 min), 10 minutes post-exercise, and 30 minutes post-exercise.
Treatment groups
120 Participants
are divided into 4 treatment groupsGroup A: Healthy, normal weight women, regular menstrual cycle, no hormones, all fitness levelsExperimental treatment 1 intervention
Group B: Healthy normal weight men, recreational fitness levelExperimental treatment 1 intervention
Group C: Healthy, overweight women, regular menstrual cycle, no hormones, recreational fitness levelsExperimental treatment 1 intervention
Group D: Healthy, overweight men, regular menstrual cycle, no hormones, recreational fitness levelsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Autophagic Flux in Peripheral Blood Mononuclear Cells (PBMCs)
Assessment of autophagic flux in PBMCs using ex vivo lysosomal inhibition and quantification of autophagy-related proteins (e.g., LC3B-II) to evaluate exercise-induced activation of autophagy pathways.
Time frame
Baseline (rest), end of aerobic warm-up phase, peak exercise, 10 minutes post-exercise, and 30 minutes post-exercise (single study day).Secondary outcomes
1
PBMC Transcriptome
Genome-wide transcriptomic profiling of PBMCs using RNA sequencing to identify exercise-induced changes in gene expression and cellular signaling pathways.
Time frame
Baseline (rest), end of aerobic warm-up phase, peak exercise, 10 minutes post-exercise, and 30 minutes post-exercise.2
PBMC Proteome
Untargeted proteomic analysis of PBMCs to characterize exercise-induced changes in protein abundance and biological pathways.
Time frame
Baseline (rest), end of aerobic warm-up phase, peak exercise, 10 minutes post-exercise, and 30 minutes post-exercise.3
PBMC Phosphoproteome
Untargeted phosphoproteomic profiling of PBMCs to assess exercise-induced changes in intracellular signaling and protein phosphorylation.
Time frame
Baseline (rest), end of aerobic warm-up phase, peak exercise, 10 minutes post-exercise, and 30 minutes post-exercise.4
Plasma Proteome
Untargeted plasma proteomics to identify circulating proteins and pathways altered by acute physical exercise.
Time frame
Baseline (rest), end of aerobic warm-up phase, peak exercise, 10 minutes post-exercise, and 30 minutes post-exercise.Sponsors and contacts
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Source ClinicalTrials.gov
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